Guido Ghilardi, Luca Paruzzo, Vrutti Patel, Jakub Svoboda, Emeline R Chong, Eugenio Fardella, Elise A Chong, Giulia Gabrielli, Sunita D Nasta, Daniel J Landsburg, Jordan Carter, Raymone Pajarillo, Stefan K Barta, Griffin White, Elizabeth Weber, Ellen Napier, David L Porter, Alfred L Garfall, Stephen J Schuster, Marco Ruella
Bendamustine has been retrospectively shown to be an effective and safe lymphodepletion regimen prior to the anti-CD19 chimeric antigen receptor T cell (CART) products tisagenlecleucel and axicabtagene ciloleucel, as well as the anti-BCMA CART products idecabtagene vicleucel and ciltacabtagene autoleucel. However, bendamustine as lymphodepletion prior to lisocabtagene maraleucel (liso-cel), a 4-1BB co-stimulated, fixed CD4:CD8 ratio anti-CD19 CART product, has not been described yet. Thus, we studied a cohort of sequentially-treated patients with large B-cell lymphomas who received bendamustine lymphodepletion before liso-cel at the University of Pennsylvania between 5/2021 and 12/2023 (n = 31)...
April 22, 2024: Journal of Hematology & Oncology
Ting Shi, Hong-Hu Zhu
The chemo-free concept represents a new direction for managing adult patients with Ph-positive acute lymphoblastic leukemia (Ph + ALL). The tyrosine kinase inhibitors (TKIs), blinatumomab and venetoclax serve as the backbone of chemo-free regimens; several prospective studies involving these drugs have demonstrated high remission rates and promising, albeit short, survival outcomes. This review summarizes the latest updates on chemo-free regimens in the treatment of adult patients with Ph + ALL, presented at the 2023 ASH annual meeting...
April 16, 2024: Journal of Hematology & Oncology
Xinxin Wang, Canrong Lu, Bo Wei, Shuo Li, Ziyu Li, Yingwei Xue, Yingjiang Ye, Zhongtao Zhang, Yihong Sun, Han Liang, Kai Li, Linghua Zhu, Zhichao Zheng, Yanbing Zhou, Yulong He, Fei Li, Xin Wang, Pin Liang, Hua Huang, Guoli Li, Xian Shen, Jiafu Ji, Yun Tang, Zekuan Xu, Lin Chen
Evidence from Europe shows that perioperative chemotherapy may be beneficial for the treatment of locally advanced gastric cancer, but reliable and robust data is lacking. To rectify this, the phase 3 RESONANCE trial investigated the efficacy and safety of S-1 plus oxaliplatin (SOX) as a perioperative chemotherapy regimen for gastric cancer. This randomized, open-label trial enrolled patients from 19 medical centers with stage II/III resectable gastric cancer who were centrally randomly assigned to either perioperative chemotherapy (PC) arm or adjuvant chemotherapy (AC) arm...
April 8, 2024: Journal of Hematology & Oncology
Qiang Lu, Dongquan Kou, Shenghan Lou, Milad Ashrafizadeh, Amir Reza Aref, Israel Canadas, Yu Tian, Xiaojia Niu, Yuzhuo Wang, Pedram Torabian, Lingzhi Wang, Gautam Sethi, Vinay Tergaonkar, Franklin Tay, Zhennan Yuan, Peng Han
Cancer immunotherapy and vaccine development have significantly improved the fight against cancers. Despite these advancements, challenges remain, particularly in the clinical delivery of immunomodulatory compounds. The tumor microenvironment (TME), comprising macrophages, fibroblasts, and immune cells, plays a crucial role in immune response modulation. Nanoparticles, engineered to reshape the TME, have shown promising results in enhancing immunotherapy by facilitating targeted delivery and immune modulation...
April 2, 2024: Journal of Hematology & Oncology
Qian Zhang, Qing Liang, Rui Zhang, Nan Wang, Xu Xiao, Jiahao Shao, Kejia Wang
The T-cell receptor (TCR) repertoires exhibits distinct signatures associated with COVID-19 severity. However, the precise identification of vaccine-induced SARS-CoV-2-specific TCRs and T-cell immunity mechanisms are unknown. We developed a machine-learning model that can differentiate COVID-19 patients from healthy individuals based on TCR sequence features with an accuracy of 95.7%. Additionally, we identified SARS-CoV-2-specific T cells and TCR in HLA-A*02 vaccinated individuals by peptide stimulation. The SARS-CoV-2-specific T cells exhibited higher cytotoxicity and prolonged survival when targeting spike-pulsed cells in vitro or in vivo...
March 27, 2024: Journal of Hematology & Oncology
Guangcai Zhong, Ran Kong, Shi Feng, Cong Wang, Qingbo Hao, Weilin Xie, Xiangxiang Zhou
Protein degraders, emerging as a novel class of therapeutic agents, have gained widespread attention due to their advantages. They have several advantages over traditional small molecule inhibitors, including high target selectivity and ability to target "undruggable" targets and overcome inhibitor drug resistance. Tremendous research and development efforts and massive investment have resulted in rapid advancement of protein degrader drug discovery in recent years. Here, we overview the latest clinical and preclinical updates on protein degraders presented at the 2023 ASH Annual Meeting...
March 22, 2024: Journal of Hematology & Oncology
Manni Wang, Siyuan Chen, Xuemei He, Yong Yuan, Xiawei Wei
Inflammation has accompanied human beings since the emergence of wounds and infections. In the past decades, numerous efforts have been undertaken to explore the potential role of inflammation in cancer, from tumor development, invasion, and metastasis to the resistance of tumors to treatment. Inflammation-targeted agents not only demonstrate the potential to suppress cancer development, but also to improve the efficacy of other therapeutic modalities. In this review, we describe the highly dynamic and complex inflammatory tumor microenvironment, with discussion on key inflammation mediators in cancer including inflammatory cells, inflammatory cytokines, and their downstream intracellular pathways...
March 22, 2024: Journal of Hematology & Oncology
Kai He, Maryam Baniasad, Hyunwoo Kwon, Tomislav Caval, Gege Xu, Carlito Lebrilla, Daniel W Hommes, Carolyn Bertozzi
Cancer early detection and treatment response prediction continue to pose significant challenges. Cancer liquid biopsies focusing on detecting circulating tumor cells (CTCs) and DNA (ctDNA) have shown enormous potential due to their non-invasive nature and the implications in precision cancer management. Recently, liquid biopsy has been further expanded to profile glycoproteins, which are the products of post-translational modifications of proteins and play key roles in both normal and pathological processes, including cancers...
March 22, 2024: Journal of Hematology & Oncology
Fahan Ma, Yan Li, Chan Xiang, Bing Wang, Jie Lv, Jinzhi Wei, Zhaoyu Qin, Yan Pu, Kai Li, Haohua Teng, Subei Tan, Jinwen Feng, Zhanxian Shang, Yunzhi Wang, Sha Tian, Changsheng Du, Yuchen Han, Chen Ding
Immunotherapy is the first-line therapy for esophageal squamous cell carcinoma (ESCC), yet many patients do not respond due to drug resistance and the lack of reliable predictive markers. We collected 73 ESCC patients (including discovery cohort and validation cohort) without immune thrombocytopenia and undergoing anti-PD1 immunotherapy. Proteomic and phosphoproteomic analysis of 73 ESCC treatment-naive samples by mass spectrometry-based label-free quantification were applied to explore the potential resistant and sensitive mechanisms, and identify predictive markers of ESCC immunotherapy...
March 15, 2024: Journal of Hematology & Oncology
Young Jun Kim, Won-Yeop Rho, Seung-Min Park, Bong-Hyun Jun
Liquid biopsy, which is a minimally invasive procedure as an alternative to tissue biopsy, has been introduced as a new diagnostic/prognostic measure. By screening disease-related markers from the blood or other biofluids, it promises early diagnosis, timely prognostication, and effective treatment of the diseases. However, there will be a long way until its realization due to its conceptual and practical challenges. The biomarkers detected by liquid biopsy, such as circulating tumor cell (CTC) and circulating tumor DNA (ctDNA), are extraordinarily rare and often obscured by an abundance of normal cellular components, necessitating ultra-sensitive and accurate detection methods for the advancement of liquid biopsy techniques...
March 14, 2024: Journal of Hematology & Oncology
Zeda Zhao, Juliang Qin, Ying Qian, Chenshen Huang, Xiaohong Liu, Ning Wang, Liqin Li, Yuqing Chao, Binghe Tan, Na Zhang, Min Qian, Dali Li, Mingyao Liu, Bing Du
BACKGROUND: Emerging evidences suggest that aberrant metabolites contributes to the immunosuppressive microenvironment that leads to cancer immune evasion. Among tumor immunosuppressive cells, myeloid-derived suppressor cells (MDSCs) are pathologically activated and extremely immunosuppressive, which are closely associated with poor clinical outcomes of cancer patients. However, the correlation between MDSCs mediated immunosuppression and particular cancer metabolism remained elusive...
February 24, 2024: Journal of Hematology & Oncology
Astrid Van den Eynde, Laura Gehrcken, Tias Verhezen, Ho Wa Lau, Christophe Hermans, Hilde Lambrechts, Tal Flieswasser, Delphine Quatannens, Gils Roex, Karen Zwaenepoel, Elly Marcq, Philippe Joye, Edgar Cardenas De La Hoz, Christophe Deben, Alessia Gasparini, Pierre Montay-Gruel, Maxim Le Compte, Eva Lion, Filip Lardon, Steven Van Laere, Vasiliki Siozopoulou, Diana Campillo-Davo, Jorrit De Waele, Patrick Pauwels, Julie Jacobs, Evelien Smits, Jonas R M Van Audenaerde
BACKGROUND: It remains challenging to obtain positive outcomes with chimeric antigen receptor (CAR)-engineered cell therapies in solid malignancies, like colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC). A major obstacle is the lack of targetable surface antigens that are not shared by healthy tissues. CD70 emerges as interesting target, due to its stringent expression pattern in healthy tissue and its apparent role in tumor progression in a considerable amount of malignancies...
February 9, 2024: Journal of Hematology & Oncology
Meilin Xue, Lei Dong, Honghai Zhang, Yangchan Li, Kangqiang Qiu, Zhicong Zhao, Min Gao, Li Han, Anthony K N Chan, Wei Li, Keith Leung, Kitty Wang, Sheela Pangeni Pokharel, Ying Qing, Wei Liu, Xueer Wang, Lili Ren, Hongjie Bi, Lu Yang, Chao Shen, Zhenhua Chen, Laleh Melstrom, Hongzhi Li, Nikolai Timchenko, Xiaolan Deng, Wendong Huang, Steven T Rosen, Jingyan Tian, Lin Xu, Jiajie Diao, Chun-Wei Chen, Jianjun Chen, Baiyong Shen, Hao Chen, Rui Su
BACKGROUND: While liver cancer stem cells (CSCs) play a crucial role in hepatocellular carcinoma (HCC) initiation, progression, recurrence, and treatment resistance, the mechanism underlying liver CSC self-renewal remains elusive. We aim to characterize the role of Methyltransferase 16 (METTL16), a recently identified RNA N6 -methyladenosine (m6 A) methyltransferase, in HCC development/maintenance, CSC stemness, as well as normal hepatogenesis. METHODS: Liver-specific Mettl16 conditional KO (cKO) mice were generated to assess its role in HCC pathogenesis and normal hepatogenesis...
February 1, 2024: Journal of Hematology & Oncology
Jian Lin, Dongning Rao, Mao Zhang, Qiang Gao
The liver is essential for metabolic homeostasis. The onset of liver cancer is often accompanied by dysregulated liver function, leading to metabolic rearrangements. Overwhelming evidence has illustrated that dysregulated cellular metabolism can, in turn, promote anabolic growth and tumor propagation in a hostile microenvironment. In addition to supporting continuous tumor growth and survival, disrupted metabolic process also creates obstacles for the anticancer immune response and restrains durable clinical remission following immunotherapy...
January 31, 2024: Journal of Hematology & Oncology
Hongying Zhang, Yongliang Liu, Jieya Liu, Jinzhu Chen, Jiao Wang, Hui Hua, Yangfu Jiang
Cancer is a complex disease resulting from abnormal cell growth that is induced by a number of genetic and environmental factors. The tumor microenvironment (TME), which involves extracellular matrix, cancer-associated fibroblasts (CAF), tumor-infiltrating immune cells and angiogenesis, plays a critical role in tumor progression. Cyclic adenosine monophosphate (cAMP) is a second messenger that has pleiotropic effects on the TME. The downstream effectors of cAMP include cAMP-dependent protein kinase (PKA), exchange protein activated by cAMP (EPAC) and ion channels...
January 17, 2024: Journal of Hematology & Oncology
Kriti Gera, Anjali Chauhan, Paul Castillo, Maryam Rahman, Akash Mathavan, Akshay Mathavan, Elizabeth Oganda-Rivas, Leighton Elliott, John R Wingard, Elias J Sayour
Myelodysplastic neoplasms (MDS) define clonal hematopoietic malignancies characterized by heterogeneous mutational and clinical spectra typically seen in the elderly. Curative treatment entails allogeneic hematopoietic stem cell transplant, which is often not a feasible option due to older age and significant comorbidities. Immunotherapy has the cytotoxic capacity to elicit tumor-specific killing with long-term immunological memory. While a number of platforms have emerged, therapeutic vaccination presents as an appealing strategy for MDS given its promising safety profile and amenability for commercialization...
January 8, 2024: Journal of Hematology & Oncology
Lawrence W Liu, Mei Wang, Nikhil Grandhi, Mark A Schroeder, Theodore Thomas, Kristin Vargo, Feng Gao, Kristen M Sanfilippo, Su-Hsin Chang
Herbicide and pesticide exposure [e.g., agent orange (AO)] is associated with an increased risk of multiple myeloma (MM) due to the contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, it is unclear whether TCDD/AO exposure (AO exposure hereafter) increases the risk of progression of monoclonal gammopathy of undetermined significance (MGUS) to MM. We sought to evaluate the association in a nationwide study of US Veterans. A natural language processing algorithm was used to confirm MGUS and progression to MM...
January 8, 2024: Journal of Hematology & Oncology
Claire Lacan, Jérôme Lambert, Edouard Forcade, Marie Robin, Patrice Chevallier, Sandrine Loron, Claude-Éric Bulabois, Corentin Orvain, Patrice Ceballos, Etienne Daguindau, Amandine Charbonnier, Yves Chalandon, Marc Bernard, Célestine Simand, Marie-Thérèse Rubio, Pascal Turlure, Johan Maertens, Anne Huynh, Michael Loschi, Jacques-Olivier Bay, Gaëlle Guillerm, Mustafa Alani, Cristina Castilla-Llorente, Xavier Poiré, Sylvain Chantepie, Natacha Maillard, Yves Beguin, Ambroise Marçais, Jérôme Cornillon, Jean-Valère Malfuson, Sébastien Maury, Nathalie Meuleman, Alban Villate, Mohammed-Amine Bekadja, Anouk Walter-Petrich, Nathalie Jacque, Micha Srour, Raynier Devillier, Stéphanie Nguyen
The use of peripheral blood (PB) or bone marrow (BM) stem cells graft in haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis remains controversial. Moreover, the value of adding anti-thymoglobulin (ATG) to PTCy is unknown. A total of 1344 adult patients received an unmanipulated haploidentical transplant at 37 centers from 2012 to 2019 for hematologic malignancy. We compared the outcomes of patients according to the type of graft, using a propensity score analysis...
January 7, 2024: Journal of Hematology & Oncology
Qing Wei, Peijing Li, Teng Yang, Jiayu Zhu, Lu Sun, Ziwen Zhang, Lu Wang, Xuefei Tian, Jiahui Chen, Can Hu, Junli Xue, Letao Ma, Takaya Shimura, Jianmin Fang, Jieer Ying, Peng Guo, Xiangdong Cheng
Antibody-drug conjugates (ADCs) represent an important class of cancer therapies that have revolutionized the treatment paradigm of solid tumors. To date, many ongoing studies of ADC combinations with a variety of anticancer drugs, encompassing chemotherapy, molecularly targeted agents, and immunotherapy, are being rigorously conducted in both preclinical studies and clinical trial settings. Nevertheless, combination therapy does not always guarantee a synergistic or additive effect and may entail overlapping toxicity risks...
January 4, 2024: Journal of Hematology & Oncology
Le-Wei Zheng, Cui-Cui Liu, Ke-Da Yu
Liquid-liquid phase separation (LLPS) is a novel principle for interpreting precise spatiotemporal coordination in living cells through biomolecular condensate (BMC) formation via dynamic aggregation. LLPS changes individual molecules into membrane-free, droplet-like BMCs with specific functions, which coordinate various cellular activities. The formation and regulation of LLPS are closely associated with oncogenesis, tumor progressions and metastasis, the specific roles and mechanisms of LLPS in tumors still need to be further investigated at present...
December 18, 2023: Journal of Hematology & Oncology
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